Myocardial oxygen tension in a region of the working, in situ canine heart will be altered by perfusion with deoxygenated blood (non-ischemic hypoxia). Blood will be deoxygenated by an isolated lung or membrane oxygenator. To define the role of hypoxia per se in autoregulation of coronary flow, coronary vascular resistance will be calculated as myocardial oxygen tension (measured polarographically) is decreased by hypoxemia and by ischemia. To define the role of metabolites in this process, myocardial pH, lactate, and adenosine will be measured at equivalent degrees and durations of non-ischemic and ischemic hypoxia. The effects of hypoxia on coronary pressure-flow autoregulation, transmural flow distribution, vascular and extracellular volumes, and action of vasoactive drugs will be determined. To define the relationship between myocardial oxygen tension and contractile force (Walton-Brody strain-gauge) in non-ischemic, hypoxic myocardium will be determined and correlated with myocardial pH and concentrations of high energy phosphates and glycogen. Depletion of myocardial potassium during non-ischemic hypoxia will be studied and the effects of cardiac glycosides and antiarrhythmic drugs on this process will be examined. The role of myocardial hypoxia per se in ischemia-induced cardiac arrhythmias and fibrillation will be studied. Coronary hemodynamic parameters, potassium exchange, and myocardial contractile force and metabolite concentrations will be studied also during extended periods of non-ischemic hypoxia and during subsequent reperfusion with oxygenated blood. Results will be compared to those observed during ischemia and reperfusion.